ABSTRACT
Objective To identify molecular differences between EBVaGC and EBCnGC by omics to provide a basis for treatment options of EBVaGC. Methods Chromogenic in situ hybridization was used to detect EBV RNA status of surgical specimens and PDXs. Targeted capture sequencing and protein mass spectrometry were implemented to analyze the different molecules, verify the PD-L1 expression by immunochemistry in EBV positive and negative tis-sues. Results Compared with EBVnGC, the higher PIK3CA mutation rate and lower TP53 mutation rate were found in EBVaGC. Post-transcriptional regulation molecules were up-regulated and molecules associated with me-tabolism and oxidative phosphorylation were down-regulated in EBVaGC. PD-L1 expression in EBV positive PDXs was significantly higher than that in EBV negative (76.92% vs 25.0%, P＜0.05). Conclusions There is a great difference between EBVaGC and EBVnGC on genetic variation and expression, which provides the basis for further exploration of the molecular mechanism and treatment strategy of EBVaGC.
ABSTRACT
Objective To establish the paclitaxel-resistant gastric cancer cell(HGC-27/PTX) and to investigate the changes of characteristics before and after resistance,as well as the possible resistant mechanisms.Methods The paclitaxel-resistant gastric cancer cell HGC-27/PTX was established by increasing paclitaxel dose gradually and intermittently.The IC50 (50% inhibitory concentration) and cell cycle were determined by CCK-8 assay and flow cytometry,respectively.The differentially expressed genes (DEGs) and signaling pathways were analyzed using RNAseq.Results The establishment of HGC-27/PTX cells lasted 9 months,and the sensitivity of paclitaxel of HGC-27/PTX cells was significantly lower than parental cells (P<0.05).Compared to parental cells,the morphology of HGC-27/PTX cells was slightly different,and the proportion of S and G2/M phase was obviously increased (P<0.01).A total of 274 DEGs were identified between the resistant and parental cells with 130 genes up-regulated and 144 genes down-regulated.DEGs were significantly enriched in extracellular matrix (ECM)-receptor interaction(P<0.001) and PI3K-Akt signaling pathways (P<0.05),which could provide evidences for reversing paclitaxel resistance.Conclusions The paclitaxel-resistant gastric cancer cells HGC-27/PTX was established with stable culturein vitro,which provides an ideal model for future study on the mechanism of drug resistance.